rs7990537

Variant names:

• chr13-35364094-A-G
• rs7990537
• NM_001385012.1:c.6179+11771A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385012.1(NBEA):​c.6179+11771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,772 control chromosomes in the GnomAD database, including 8,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8300 hom., cov: 32)
• Consequence: NBEA NM_001385012.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 1 publications found

Genes affected

NBEA (HGNC:7648): (neurobeachin) This gene encodes a member of a large, diverse group of A-kinase anchor proteins that target the activity of protein kinase A to specific subcellular sites by binding to its type II regulatory subunits. Brain-specific expression and coat protein-like membrane recruitment of a highly similar protein in mouse suggest an involvement in neuronal post-Golgi membrane traffic. Mutations in this gene may be associated with a form of autism. This gene and its expression are frequently disrupted in patients with multiple myeloma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants may exist, but their full-length nature has not been determined.[provided by RefSeq, Feb 2011]

NBEA Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with or without early-onset generalized epilepsy

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: STRONG Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385012.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	NM_001385012.1	MANE Select	c.6179+11771A>G		intron	N/A	NP_001371941.1
	NBEA	NM_001379245.1		c.6170+11771A>G		intron	N/A	NP_001366174.1
	NBEA	NM_015678.5		c.6179+11771A>G		intron	N/A	NP_056493.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEA	ENST00000379939.7	TSL:5 MANE Select	c.6179+11771A>G		intron	N/A	ENSP00000369271.2
	NBEA	ENST00000400445.8	TSL:5	c.6179+11771A>G		intron	N/A	ENSP00000383295.3
	NBEA	ENST00000688626.1		c.4025+11771A>G		intron	N/A	ENSP00000509239.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44181 AN: 151654 Hom.: 8282 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44253 AN: 151772 Hom.: 8300 Cov.: 32 AF XY: 0.288 AC XY: 21362 AN XY: 74218

African (AFR) AF: 0.536 AC: 22214 AN: 41406

American (AMR) AF: 0.217 AC: 3294 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3462

East Asian (EAS) AF: 0.224 AC: 1158 AN: 5172

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4822

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10610

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12931 AN: 67796

Other (OTH) AF: 0.260 AC: 548 AN: 2110

Alfa AF: 0.249 Hom.: 797

Bravo AF: 0.306

Asia WGS AF: 0.262 AC: 910 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.84
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7990537; hg19: chr13-35938231;